Dr Rhonda Voskuhl Outlines the Importance of Studying Sex Differences in MS

Sex differences in multiple sclerosis (MS) has been known for some time, and studying these differences benefit both sexes, explained Rhonda Voskuhl, MD, Jack H. Skirball chair of MS research, director of the MS program, and professor of neurology at the University of California, Los Angeles.

Why is studying sex differences in multiple sclerosis important?
Sex differences are becoming very important. The NIH [National Institutes of Health] has now mandated that all grants include both sexes, because we can’t study one sex and then assume it’s true in the other. And this has come up in other situations. It started, some of it, even in the dose of aspirin to prevent heart attacks was based on the dose for males and then for females it was different. And also, the dose of Ambien came up. The dose of Ambien, just a sleep aid, is too high for women. When women take that dose, they feel really drugged and drowsy the next day, they get in their cars, they go to work, and some of these things came up and said we really need to tailor our drug development and not assume that all the things that are optimized for one sex are true for the other.

That’s the trials level. And that’s being done and that’s good. For safety reasons and efficacy—it may work better in one than the other or the dose may differ or the toxicity may differ in one versus the other. Now, at the basic science level, people were still doing, like a lot of the neuroscience, was being done in male rats and mice, and then these findings would come through and they say, “Great, this is the way to fix the disease,” but they didn’t do those studies in the females. Or some of the MS stuff, they did it in the females, but they didn’t do it in the males.

And the view of the NIH now is, and they’re right, is that we can’t just assume what’s true in one sex is for the other, and so you have to do, in every NIH grant, you have to consider both sexes. It’s called sex as a biologic variable. It’s got to be considered in all of these experiments. And my view is, it’s a win-win, because you’ll either find out that whatever you found is not only true in one, it’s true in the other, so now you’re finding is even bigger, or you’ll find that it’s not true in the other, and then you’ll have a sex difference. And that’s a good thing, actually, to discover sex differences, in the sense that you can then figure out what makes the disease better or worse, because it’s obviously being controlled by either sex hormones or sex chromosomes—these are the sex differences.

So, in MSwhat we’ve done, focusing on MS, sex differences were known for a long time, whereby females are more susceptible to MS than males, it’s about 3 to 1, and also males actually do worse once they get the disease. It’s odd how they’re less susceptible and they have less inflammatory response, but when males get the disease, they [do] have worse disability progression.

So, within MS there’s 2 very important things. One is why do females get the disease more often than men, if we understood that we could, particularly in females, try to prevent that. The other thing is when males get MS, they do worse with disability progression, if we understood that we could come in with a treatment to then try to block whatever is making the males worse. So, it’s relevant to both sexes just to study the other, you just learn when you know more and can compare them.
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